The effect of isoflurane on unmyelinated and myelinated fibres in the rat brain

Abstract

The effect of isoflurane on unmyelinated and myelinated fibres of the rat brain was investigated in vitro. The amplitude of the unmyelinated fibre potential (the prevolley of the hippocampal CA1 region) was reduced in a dose-dependent manner with increasing isoflurane concentrations (up to 5%). The conduction velocity was slightly decreased. The minimal alveolar concentration (MAC) anesthetizing 50% of the animals is 1.38%. At this concentration the presynaptic volley was reduced by 18% and the conduction velocity was decreased by about 1%. The effect on myelinated fibres (fimbria) was small and significantly different from the effect on unmyelinated fibres (P = 0.03 and 0.005 at 1 and 2% isoflurane, respectively.

Sevoflurane depolarizes pre‐synaptic mitochondria in the central nervous system

“…Postsynaptic neurone. Clinically relevant doses of isoflurane depress impulse conduction in thin, unmyelinated, afferent nerve fibres, whereas almost no effect is found on impulse propagation in thicker, myelinated fibres (11). Furthermore, isoflurane hyperpolarizes the postsynaptic neuron (12), making the cell more refractory to membrane depolarisation.…”

Effects of halothane and enflurane on firing threshold of frog myelinated axons.

“…In hippocampal slices from mice increased threshold of both myelinated and unmyelinated fibres was inferred from changes in amplitude of compound potentials during constant focal stimulation in the presence of diethyl ether and isoflurane (Berg-Johnsen & Langmoen, 1986). In myelinated fibres of the hippocampal fimbria exposed to as much as 5 % isoflurane, no increase in latency of compound potentials was seen, and the increase observed in latency of the peak from unmyelinated fibres of stratum radiatum was only 8 %.…”

“…Actions on activity dependence: relation to neural mechanisms of general anaesthesia At the neural level, hypotheses for the mechanism(s) of general anaesthesia include: reduction in EPSP number and amplitude either by reduced release of transmitter at nerve terminals (Richards, 1973(Richards, , review 1983; or by reduced sensitivity of postsynaptic membrane and of chemically gated conductances to transmitters and modulators (Gissen, Karis & Nastuk, 1966;Richards, Russell & Smaje, 1975;Gage & Robertson, 1985); prolongation of GABAergic IPSPs or other potentiation of inhibition (Nicoll, 1972;review, Krnjevic, 1986); altered slow synaptic events and secondary messengers (review, Kendig & Trudell, 1982); presynaptic conduction failure in axon trunks, at axon branches (Grossman & Kendig, 1982) and in fine unmyelinated branches of axonal teledendra (Larrabee & Posternak, 1952;Berg-Johnsen & Langmoen, 1986); selective dynamic blockade of active fibres due to use-dependent blocking action of inhalational agents (Strichartz, 1980;Grossman & Kendig, 1982); selective sensitivity of cell groups and brain regions such as reticular activating system or other central integrative systems (French, Verzeano & Magoun, 1953;Wall, 1967); and various other ideas that share a focus on reduction of neural signals without much discussion of how such a reduction might result in the clinical attributes of anaesthesia.…”

Emergence of spatially heterogeneous burst suppression in a neural field model of electrocortical activity

“…While peripherally it is generally assumed that anesthetics principally depress spinal motoneuron excitability, as assessed by reductions in F-wave amplitudes (Friedman et al, 1996; Rampil and King, 1996), there are a number of reports documenting the significant effects of anesthetic agents in either increasing (cyclopropane, nitrous oxide, diethyl ether) (Rosner et al, 1971) or reducing (pentobarbital, desflurane, enflurane, halothane) (Rampil and King, 1996; Oh et al, 2010; Nowicki et al, 2013) nerve conduction velocity at clinical levels, as assessed by increases in F-wave latency. Centrally, there is some evidence that volatile anesthetics may preferentially depress nerve conduction in unmyelinated axons (Berg-Johnsen and Langmoen, 1986; Mikulec et al, 1998). For instance, isoflurane was found to induce a conduction block in 20–30% of the unmyelinated fibers in the CA1 region of the rat hippocampus at clinical concentrations, as well as having a 1% effect on the actual conduction velocity (Berg-Johnsen and Langmoen, 1986).…”

“…Centrally, there is some evidence that volatile anesthetics may preferentially depress nerve conduction in unmyelinated axons (Berg-Johnsen and Langmoen, 1986; Mikulec et al, 1998). For instance, isoflurane was found to induce a conduction block in 20–30% of the unmyelinated fibers in the CA1 region of the rat hippocampus at clinical concentrations, as well as having a 1% effect on the actual conduction velocity (Berg-Johnsen and Langmoen, 1986). On the basis of empirical evidence indicating that the cortico-cortical fiber system is comprised of a mixture of myelinated and unmyelinated fibers, cf.…”